This competing continuation of a Senior Scientist Award (K05) will allow the applicant to conduct research on cessation and reduction of tobacco and marijuana use and on new methods to treat nicotine and cannabis dependence. The K05 would allow the PI to continue leadership roles in organizations interested in tobacco research and tobacco control and to continue science education activities such as mentoring and teaching. The applicant's past research contributions include description of the nicotine withdrawal syndrome, psychiatric co-morbidity with nicotine dependence, abuse liability of nicotine replacement, the role of expectancies in nicotine effects, caffeine reinforcement and dependence, and harm reduction approaches to nicotine dependence. The applicant founded the Human Behavioral Pharmacology Laboratory at the University of Vermont (UVM) and co-founded the Society for Research on Nicotine and Tobacco and the Association for the Treatment of Tobacco Use and Dependence. In the prior K05, the applicant averaged 13 published papers/yr of which he was first author on 9/yr and of which 7/yr were empirical studies. UVM has several resources to aid the applicant to learn new disciplines and methods; e.g. UVM currently has 25 NIH grants on drug abuse across 13 Pis. This continuation proposes tobacco studies to a) compare the efficacy of NRT-assisted abrupt vs gradual cessation, b) test a cannabinoid antagonist for smoking cessation, c) test a computer mediated clinical decision support system to help clinicians treat tobacco dependence, d) describe why the large majority of smokers do not seek free treatment and e) comprehensively review the world literature on the nicotine withdrawal syndrome. The continuation proposes a new line of research on marijuana to f) describe the natural history of attempts to stop or reduce marijuana use, g) determine if the marijuana withdrawal syndrome is due to THC deprivation, h) directly compare the clinical significance of marijuana and tobacco withdrawal syndromes, i) describe marijuana withdrawal in treatment seekers and j) describe marijuana withdrawal in adolescent marijuana users. The continuation will also include collaborating with other drug abuse researchers at UVM and elsewhere. The applicant will continue to mentor 4-6 students/yr and to be actively engaged in media and policy initiatives.